The purpose of this proposal is two-fold: (1) to develop synthetic routes to 2'-deoxy C-nucleosides that are concise, employ readily available starting materials and result in intermediates that are conveniently transformable to a series of biologically interesting target compounds, and (2) to biologically evaluate these compounds with regard to their cytotoxic propensities in order to determine which compounds may exhibit promising antineoplastic activity and therefore should be explored further. By applying synthetic procedures currently in use in other areas of organic chemistry, we believe that we will be able to develop versatile routes to 2'-deoxy C-nucleosides that will allow the realization of a series of derivatives of this class of compounds. The availability of a series of 2'-deoxy C-nucleosides will then allow a meaningful preliminary evaluation of their antineoplastic properties. The biological data accrued will, in turn, indicate which compounds warrant further study and what future, long-term directions our program should take. The significance of this program is three-fold: (1) because of its versatility and potential for extrapolation, the methodology developed as part of this proposal will contribute significantly to the medicinal chemist's synthetic resources; (2) the potential antitumor activity associated with the products developed in this proposal may well result in significant contributions toward the search for new compounds for the treatment of neoplastic diseases; and (3) realization of the target compounds proposed in this program will allow a rational assessment of the structure-activity relationships exhibited by the pyrimidine-like 2'-deoxy C-nucleoside series of compounds.